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Direct contractile effect of motilin on isolated smooth muscle cells from human gallbladder.

To test the hypothesis that motilin receptors are present on smooth muscle cells of the human gallbladder, smooth muscle cells were isolated from the gallbladder and their direct contractile responses to motilin were examined. Motilin elicited a dose-dependent contraction of human gallbladder smooth muscle cells. Maximal contraction rate as defined by the percentage decrease in cell length was 23.7 +/- 0.7% at 10(-7) M for motilin and was similar to that for cholecystokinin octapeptide (CCK-OP) (24.2 +/- 1.5%) observed at 10(-10) M. The contractile sensitivity of gallbladder muscle cells to motilin (ED50 = 6 pM) was two orders of magnitude less than that to CCK-OP (ED50 = 0.07 pM). The motilin-induced contraction was inhibited in a dose-dependent manner by addition of 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride, an inhibitor of intracellular Ca2+ release. These results indicate that distinct motilin receptors are likely to be present on human gallbladder smooth muscle cells, as evidenced by their direct contractile responses, and suggest that Ca2+ release from intracellular calcium stores is important in the contractile response to motilin.

Calcium↗

Impaired release of gallbladder calcitonin gene-related peptide in human gallstone disease.

Calcitonin gene-related peptide (CGRP) is a neurotransmitter present in the peripheral ends of sensory neurons of the gut and may modulate reflexes of the enteric nervous system. We studied the release of CGRP in normal human gallbladders and in those containing gallstones to test the hypothesis that abnormalities of regulation of CGRP release participate in gallstone formation. Human gallbladder strips were obtained from histologically normal organs removed during liver surgery (n = 8) or from patients operated upon for symptomatic cholelithiasis (n = 14). After removal of the mucosa, muscle strips were superfused with oxygenated Kreb's buffer in an organ bath at 37 degrees C. Pharmacologic agents were added to the superfusate and samples were collected at 2-min intervals for analysis. CGRP release was measured by a sensitive and specific radioimmunoassay and adjusted for tissue weight. In normal gallbladders, CGRP release was stimulated sixfold over basal by capsaicin (10(-5) M) to 363 +/- 75 pg per gram of muscle per 2 min. This release was abolished by addition of somatostatin (SS) or the neural blocker tetrodotoxin (TTX). Lesser degrees of CGRP release were observed after nonspecific stimulation with K+ or phosphodiesterase inhibition with caffeine. In gallbladders with gallstones, capsaicin-induced CGRP release was 74 +/- 16 pg per gram of muscle per 2 min (20% of normal, P < 0.001). Release induced by caffeine and K+ was also inhibited compared to normal gallbladder strips. Release of CGRP from diseased strips was abolished by TTX and inhibited by SS to degrees similar to normal tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitonin Gene-Related Peptide↗

Relation between postoperative infections and gallbladder bile leakage during laparoscopic cholecystectomies.

BACKGROUND: In 1,577 laparoscopic cholecystectomies, 111 due to acute and 1,466 due to chronic cholecystitis, the incidence of intraoperative gallbladder rupture and its relationship with abdominal wound infections were evaluated. METHODS: A sampling test for binomial proportions and a binomial approximation test for discrete data were employed for statistical analysis. Gallbladder accidental opening took place in 250 (19%) out of the 1,466 chronic and in 44 (40%) out of the 111 acute cholecystitis, disclosing a statistically significant difference (p < 0.01). Postoperatively, there were 32 (2%) surgical wound infections, 17 (1.3%) in the absence of gallbladder injury and 15 (5%) when gallbladder injury was observed, likewise showing a statistically significant difference (p < 0.05). RESULTS: It should be pointed out that all 32 wound infections involved the umbilical incision, of which 3 with chronic suppuration required reintervention where remnants of stones were found in the parietal route. The seven with symptomatic abdominal fluid resolved without specific treatment. As regards the seven intraabdominal infections, two remitted with antibiotics and five required percutaneous drainage. There was no significant correlation between the presence of cavity fluid abdominal collections or infections and bile spillage. CONCLUSION: Gallbladder injury proved more frequent in laparoscopic cholecystectomies performed due to acute cholecystitis, while bile spillage increased the incidence of umbilical wound infection, particularly in the presence of remnants of stones, but there was no correlative increase in the incidence of intraabdominal collections or infections.

Acute Disease↗

Fluid transport and dimensions of epithelial cells and intercellular spaces in frog gallbladder. Studies in the living state, and during processing for electron microscopy.

Morphologic findings of widely dilated intercellular spaces in fluid transporting epithelia have been claimed as evidence for the existence of an epithelial compartment in which the coupling between solute and water fluxes takes place. The validity of using epithelial geometry in sectioned material as an argument can be questioned. The present report describes the morphological appearance of frog gallbladder epithelium--normal and ouabain-treated--in the living state in vitro and after fixation, dehydration and embedding. Gallbladder segments were photographed in the living state and at the end of each step of the preparative procedure. Direct observations of whole-mounted gallbladder segments were carried out, taking advantage of the possibility of optical sectioning and high resolution by Nomarski-microscopy. The same specimens were then sectioned and examined by conventional light and electron microscopy. The observations were quantitated and showed that the epithelial cells of normal and ouabain-treated gallbladders experienced an average linear shrinkage down to 70% of their length in Ringer's solution, which corresponds to a volume shrinkage down to 35%. Moreover, dilated lateral intercellular spaces appeared during the dehydration and embedding procedure in normal but only very moderately or not at all in ouabain-treated gallbladder specimens.

Animals↗

A patient with early gallbladder cancer derived from a Rokitanski-Aschoff sinus.

We present herein a case of a 40-year-old male with early gallbladder cancer derived from a Rokitanski-Aschoff sinus (RAS). The patient originally presented at our hospital with epigastric discomfort, following which a diagnosis of adenomyomatosis (ADM) of the gallbladder was made, and a cholecystectomy performed. Histopathological examination of the resected specimen revealed a 7-mm well-differentiated papillo-tubular adenocarcinoma in the RAS epithelium in the body of the gallbladder. The RAS extended to the "pm" layer but the adenocarcinoma was an in situ lesion localized within the RAS epithelium. Considering the difficulties in making an early diagnosis of gallbladder cancer, active surgery should be performed for patients in whom ADM is seen in the gallbladder.

Adenocarcinoma, Papillary↗

A developmental study of the localization of NADPH-diaphorase in the ganglionated plexus of the guinea-pig gallbladder.

A histochemical investigation of age-related changes that occur with respect to the localization of NADPH-diaphorase in the ganglionated plexus of the guinea-pig gallbladder was carried out. In all age groups examined (embryonic stages day 34 and 52, 2 to 4-day old, 6-month old and 2-year old), the mean percentage of NADPH-diaphorase-positive neurons per ganglion was obtained by taking the number of neurons that were immunoreactive to protein gene product 9.5 (a general neuronal marker) as 100%. In addition, the possible co-existence of NADPH-diaphorase and nitric oxide synthase in the ganglionated plexus of 2 to 4-day old and 6-month old guinea-pig gallbladder was investigated. NADPH-diaphorase was not present in the ganglionated plexus of the gallbladder at embryonic day 34. At embryonic day 52, all the protein gene product 9.5-immunoreactive neurons showed positive staining to NADPH-diaphorase; this dropped to a minimum at 2-4 days (26.7%), rose slightly at 6 months (33.6%), and finally returned close to the 100% value at 2 years. In the gallbladders of 2-year old guinea-pigs, some (3 out of 10) ganglia were devoid of protein gene product 9.5-immunoreactive neurons, but NADPH-diaphorase-stained granules were found within the ganglia. However, all those neurons that were immunopositive to protein gene product 9.5 also expressed NADPH-diaphorase. Moreover, NADPH-diaphorase-positive neurons in the gallbladder of 2 to 4-day-old and 6-month-old guinea-pigs were found to express nitric oxide synthase.

Aging↗

Effect of cholinergic agonists and antagonists on gallbladder volume in fasting man.

The effect of direct cholinergic stimulation and blockade on gallbladder volume, determined by real-time ultrasonography (RUS), was evaluated in twenty normal, fasting subjects. Eleven subjects received atropine sulphate or placebo and 9 subjects a series of 3 injection of prostigmine, bethanechol or placebo, randomly assigned, at intervals of 24 h. RUS was performed under basal conditions after fasting for 12 h and every 5 min after drug injection up to 45 min in the atropine study and up to 60 min after prostigmine and bethanechol. There was no significant variation from fasting gallbladder volume after placebo in either group. After atropine sulphate gallbladder volume at first decreased and then significantly increased. With bethanechol and prostigmine, the volume fell significantly to a trough after 30 to 35 min, and then it returned to the basal value within 60 min. It is suggested that cholinergic mediation is involved in maintaining fasting tone in the gallbladder and that cholinergic stimulation causes contraction of the gallbladder by a direct effect.

Adult↗

Effects of hydrostatic pressure on fluid transfer by the isolated gallbladder.

The influence of hydrostatic pressure elevation on fluid absorption by the isolated guinea pig gallbladder was determined following addition of various smooth muscle spasmogens to the serosal bathing medium. Acetylcholine, prostaglandin E1 and ouabain increased intraluminal pressure from about 4 cm H2O to 13 cm H2O. The pressure increase was associated with a marked but transient stimulation in fluid transfer. The same phenomenon was observed following an increase in hydrostatic pressure by addition of Ringer's solution to the gallbladder lumen. Evidence is presented to support the hypothesis that this phenomenon represents the extrusion of an edema from the gallbladder wall. Two observations favour this explanation: 1. The wet weights of gallbladder subjected to high intraluminal hydrostatic pressure were only one third of those at low pressure. 2. Microscopic examination of the wall of gallbladders at low pressure showed a marked submucosal edema.

Acetylcholine↗

Alleviation of gallbladder complications by treatment of hepatic arterial embolization with caerulein.

Transcatheter arterial embolization (TAE) with the concurrent use of caerulein was assessed for the purpose of preventing gallbladder complications often seen after TAE of hepatic carcinoma. Ninety-six cases with primary hepatic carcinoma, who had undergone TAE in the right hepatic arterial region over the past 4 years, were divided into three groups: 22 cases for which embolization was possible on a selective basis by passing the catheter to the peripheral side beyond the bifurcated region of the cystic artery; 40 cases who had undergone TAE in which caerulein was not administered, from the central side of the bifurcated region of the cystic artery; and 34 cases given 20 micrograms caerulein 15-30 min before TAE. A comparison was made using the abdominal pain, pyrexia, rate of leukocytosis and the US findings of the gallbladder as the indices of the gallbladder complications. As a result, it became evident that it was possible to prevent or alleviate gallbladder complications if caerulein were administered before TAE in cases where the embolizing substances were infused in the right hepatic artery from the central side of the bifurcated region of the cystic artery. It was conclusively shown that the gallbladder blood flow decreases if the organ is contracted by caerulein, which in turn causes a decrease in the inflow of the embolizing substances whereby complications are alleviated.

Adult↗

Trends in management of gallbladder disorders in children.

Gallbladder disorders have been recognized with increasing frequency in pediatric patients. This study aimed to identify recent trends in management and compare the effectiveness of laparoscopic (LC) over open cholecystectomy (OC) by a retrospective chart analysis of all cholecystectomies from 1990 through 1995. Information obtained included demographics, symptoms, predisposing conditions, associated illnesses, family history, imaging studies, type of cholecystectomy, complications, operative time, pain medication, diet recommencement, pathologic findings, and length of hospital stay. The type of cholecystectomy (OC vs. LC) was compared with the clinical variables using standard statistics. Eighty-three patients between 21 months and 18 years of age were identified; their mean age was 14.8 years. Females (76%) with classic biliary symptoms predominated;12% of the patients developed gallstone pancreatitis and 7% jaundice. Abnormal liver chemistry values, obesity, and elevated triglyceride levels comprised the most significant predisposing factors. Indications for surgery were cholelithiasis in 71 patients (86%), gallbladder dyskinesia in 10 (12%), and sludge/polyp in 2. Fifty-nine cholecystectomies (71%) were done laparoscopically and 24 (29%) open. Choledocholithiasis in 6 children (7%) was managed by open extraction with t-tube placement or endoscopic papillotomy followed by LC. No major ductal complication was identified. The predominant pathologic finding was chronic cholecystitis, including the subgroup with biliary dyskinesia. Statistical comparison showed that LC is superior to OC in regard to length of stay, diet resumption, use of pain medication, operating time, and cosmetic results. It is concluded that a contemporary diet, obesity, and abnormal liver chemistry are the main predisposing conditions of gallbladder disease in children in this decade. Females in their teenage years with typical symptoms continue to be the most commonly affected group. Persistent biliary symptoms associated with low gallbladder ejection fractions during hepatobiliary cholecystokinin-stimulated scans can be caused by dyskinesia. The method of choice to remove the diseased gallbladder in children is LC, which is safe, efficient, and superior to the conventional method. Common duct stones can be managed by simultaneous endoscopic papillotomy. The costs of LC are reduced by employing reusable equipment and selective cholangiographic indications.

Adolescent↗

Elemental diet stimulates gallbladder contraction and secretion of cholecystokinin and pancreatic polypeptide in man.

This study was undertaken to investigate the effect of ingestion of 80 g Vivonex on gallbladder volume, plasma cholecystokinin (CCK), and pancreatic polypeptide (PP) in eight healthy volunteers and to compare the results with those obtained after ingestion of 60 ml corn oil. Gallbladder volumes were measured by ultrasonography. Plasma CCK was determined by radioimmunoassay using region-specific antibodies; antibody 1703 binds to COOH-terminal CCK-peptides containing at least 14 amino acid residues, while antibody T204 binds to COOH-terminal CCK-peptides containing the sulfated tyrosine region. Plasma PP was also measured by radioimmunoassay. Ingestion of Vivonex induced significant increases in plasma CCK (0.6 +/- 0.1 to 4.6 +/- 0.6 pM, antibody 1703; 1.8 +/- 0.3 to 5.9 +/- 0.5 pM, antibody (T204; P less than or equal to 0.0005) and decreases in gallbladder volume (21.4 +/- 2.8 to 11.2 +/- 2.3 cm3; P = 0.0001). Integrated plasma CCK secretion and gallbladder contraction after Vivonex were not significantly different from the results found after corn oil. Both Vivonex and corn oil-induced small increases in plasma PP. We conclude that Vivonex is a potent stimulus for the secretion of CCK and contraction of the gallbladder.

Adult↗

Metastatic carcinoma of the gallbladder from renal cancer presenting as intraluminal polypoid mass.

We report a rare case of secondary involvement of the gallbladder by metastatic renal cell carcinoma. A 71-year-old man was diagnosed as having a polypoid mass within the gallbladder when he underwent right nephrectomy for a renal cell carcinoma. A preoperative diagnosis of simultaneous carcinoma of the gallbladder was made, and extended cholecystectomy with regional lymphadenectomy was performed five months after the initial operation. Postoperative histological examination of the polypoid mass within the gallbladder and a pancreatic mass excised during the second surgery revealed these resected tumors to be identical to the clear cell type of renal cell carcinoma. We feel that this case presents synchronous involvement of the gallbladder and pancreas by metastatic renal cell carcinoma of the right kidney.

Aged↗

Gallbladder dyskinesia in chronic acalculous cholecystitis.

To test the hypothesis that there is an early stage of cholesterol gallstone formation in man characterized by symptoms of chronic cholecystitis, poor gallbladder emptying, and biliary cholesterol crystals, we studied cholecystokinin-stimulated gallbladder emptying by DISIDA scintigraphy and examined bile for cholesterol crystals in symptomatic patients with normal oral cholecystography and gallbladder sonography. Of 36 patients studied, 16 had biliary cholesterol crystals; their mean 30-min gallbladder ejection fraction was 25.9 +/- 14.8%. Among the 20 patients without crystals, the mean ejection fraction was 60.3 +/- 23.3%. Fifteen patients, 11 with crystals and four without, had cholecystectomy because of persistent symptoms. All with crystals preoperatively and three without had chronic cholecystitis histologically. One patient without crystals had normal histology. We conclude that poor gallbladder contractility, well-established as an etiologic factor in animal models of cholesterol cholelithiasis, is now linked to acalculous cholecystitis, an early stage of human cholesterol cholelithiasis.

Adult↗

Alterations in biliary motility correlate with increased gallbladder prostaglandin synthesis in early cholelithiasis in prairie dog.

Abnormal biliary motility has been observed in humans with gallstones and in animal models; however, the mechanism by which these abnormalities occur remains unknown. In this study we investigated the relationship between cholesterol gallstone formation, changes in biliary motility, and rates of gallbladder prostaglandin synthesis in prairie dogs receiving a 0.34% cholesterol diet for two, four, or six weeks. Gallstones did not occur until four weeks, when the incidence was 14%; after six weeks the incidence was 64%. Gallbladder emptying increased slightly at two weeks before becoming significantly decreased at four and six weeks. In contrast, there was a near linear increase in basal cystic duct resistance which began by two weeks of cholesterol feeding, although sphincter of Oddi resistances remained normal throughout the period of study. The synthesis of prostaglandins E and F2 alpha by the gallbladder was also increased beginning at two weeks and rose to a plateau at four and six weeks. In view of the potent effects of prostaglandins on biliary smooth muscle, these findings suggest that prostaglandins may mediate early changes in gallbladder and cystic duct motility which ultimately result in impaired gallbladder emptying.

Animals↗

Diagnosis of gallbladder perforation in acute acalculous cholecystitis in critically ill patients.

In the presence of ascites ultrasound is not appropriate to distinguish between gallbladder perforation and acute acalculous cholecystitis. However, the correct and early diagnosis of gallbladder perforation is important for the treatment and prognosis. We report 4 critically ill patients with ascites. All patients had evidence of gallbladder perforation by ultrasound and underwent cholecystectomy: 2 patients had gallbladder perforation, but 2 had acalculous cholecystitis without perforation. Markedly elevated serum alkaline phosphatase was the only discriminating finding indicating gallbladder perforation.

Adult↗

The source and action of histamine in the isolated guinea-pig gallbladder.

We have investigated the effects of histamine on motility of the gallbladder and characterized the receptor types involved. Histamine and the histamine H1-receptor agonist, 2-thiazolylethylamine (2-TEA) contracted the isolated guinea-pig gallbladder strip in a dose dependent manner. The contractile response to histamine was shifted to the right by the H1-receptor antagonist, mepyramine. In pre-contracted gallbladder strips, the H2-receptor agonist dimaprit reduced the tension generated in a dose dependent fashion. The histamine H2-receptor antagonist, ranitidine shifted the histamine concentration effect curve to the left and attenuated the dose dependent relaxations elicited at high concentrations. The histamine H3-receptor agonist, (R)-alpha-methylhistamine (RMHA) elicited dose dependent contraction of the tissue which was significantly inhibited in the presence of mepyramine. The effects of electrical field stimulation (EFS) on the strips were not significantly altered by the presence of RMHA (10(-10) - 10(-7) M) indicating little pre-synaptic H3 activity in this tissue. Histamine immunoreactivity (IR) was detected in gallbladder whole mount preparations of the mucosa and the muscularis/serosa. The histamine IR appeared cell bound in cells of varying morphological characteristics but no IR was detected in nerve fibres or cell bodies (ganglia). Alcian blue staining was consistent with the distribution of histamine IR cells as mast cells. The results indicate that histamine is distributed in the guinea-pig gallbladder and it can regulate contractile activity via activation of H1 and H2 but not H3 receptors.

Animals↗

Computed tomography after ESWL of gallbladder calculi.

Computed tomography (CT) was performed on 88 patients before and after extracorporeal shock wave lithotripsy (ESWL) of gallstones to find the effects of ESWL on the gallbladder and surrounding liver tissue. Post-ESWL scans demonstrated a thickening of the gallbladder wall in 25 (28.4%) cases. In one patient an intrahepatic bilioma beside the gallbladder was seen 3 days after ESWL treatment. Hematoma of the gallbladder wall or the adjacent liver tissue was not seen, and neither a hydrops nor biliary-induced pancreatitis was observed. The authors conclude that while some patients undergoing ESWL will show some posttreatment abnormality on CT scans, the procedure is associated with a low frequency of serious gallbladder and liver trauma.

Cholecystography↗

Ultrasonographic features of primary carcinoma of the gallbladder: report of five cases.

The sonographic features of primary carcinoma of the gallbladder in five patients are presented. Two sonographic patterns were seen depending on whether or not the lumen of the gallbladder was visualized. In two patients the gallbladder lumen was visualized and an irregular fixed nonshadowing soft tissue mass was seen arising from the wall and projecting into the lumen. In the remaining three patients a solid mass was seen in the predicted location of the gallbladder without visualization of gallbladder lumen. Ancillary findings such as local involvement of liver and signs of biliary obstruction supported the diagnosis.

Aged↗